Association between Polyunsaturated Fatty Acid Profile and Bronchial Inflammation in Bronchiolitis Obliterans.

Introduction: Bronchiolitis obliterans (BO) is a chronic lung disease, which occurs after an insult to the lower airways, in particular after airway infections or after stem cell transplantation, and which results in persistent inflammation. N-3 and n-6 polyunsaturated fatty acids (PUFA) have been shown to influence the inflammatory processes in chronic inflammatory conditions. Since BO is maintained by persistent pulmonary inflammation, a disbalanced n-6/n-3 fatty acid profile could support the inflammatory process in patients with BO and therefore, could become an approach to new therapeutic options. Methods: Twenty-five patients with BO (age: 13; 7-39) and 26 healthy controls (age: 19; 7-31) participated in the study. Lung function (forced viral capacity (FVC), forced expiratory volume 1 (FEV1), residual volume (RV)), and lung clearance index (LCI) were measured. Induced sputum was analyzed for cytology and cytokine levels (IL-1ß, IL-6, IL-8, TNF-α) using cytometric bead array (CBA). The PUFA profile was determined in the serum and induced sputum by gas chromatography. Results: Patients presented with significantly lower FVC and FEV1 as well as higher RV and LCI measurements compared to the control group. Apart from a massive airway inflammation indicated by elevated numbers of total cells and neutrophils, the CBA analysis showed significantly increased levels of IL-1ß, IL-6, and IL-8. The analysis of PUFA in sputum and serum revealed a significant difference in the ratio between the n-6 PUFA arachidonic acid (AA) and the n-3 PUFA docosahexaenoic acid (DHA) (AA : DHA). Furthermore, the AA : DHA ratio significantly correlated with the inflammatory cytokines in induced sputum. Conclusion: Lung function in BO is significantly impaired and associated with uncontrolled neutrophil-dominated airway inflammation. Furthermore, the imbalance in the AA/DHA ratio in favor of n-6 PUFA demonstrates a pro-inflammatory microenvironment in the cell membrane, which correlates with the inflammatory cytokines in induced sputum and might be an option for an anti-inflammatory therapy in BO.

Year-round treatment initiation for a 6-grasses pollen allergoid in specific immunotherapy of allergic rhinoconjunctivitis and asthma.

Aim: Allergen immunotherapy (AIT) is an effective treatment for allergic diseases. We investigate whether treatment-initiation during the pollen season is safe. Methods: RCT-IIIb-trial of 6-grass-pollen-allergoid (Allergovit®) in grass pollen-allergic patients (18-65 years) with moderate-severe rhinitis/rhinoconjunctivitis (± controlled asthma), randomized 2:1 to treatment-initiation during (Group-A) versus outside the pollen season (Group-B). Results: Of 240 patients (32.8 ± 9.9 years, 19.5% asthma) treated, 84.9% (Group-A) and 86.6% (Group-B) reached maintenance dose without delay. Treatment-emergent adverse events occurred in 108 (68.4%/Group-A) and 41 patients (56.2%/Group-B) leading to premature trial-termination in 11 patients (7%/A) versus 3 (4.1%/B). Across groups, physicians (for 190 patients; 85.2%) and patients (192; 86.1%) rated the tolerability as 'very good'-'good'. Phleum pratense-specific IgG4 increased in both groups (p < 0.0001). Conclusion: Year-round allergen immunotherapy-initiation with this preparation is safe.

Real-world benefits of allergen immunotherapy for birch pollen-associated allergic rhinitis and asthma.

BACKGROUND: Real-world evidence is sparse on the benefits of allergen immunotherapy [AIT; subcutaneous/sublingual immunotherapy (SCIT/SLIT)], the only disease-modifying intervention for allergic rhinitis (AR) with long-term efficacy. This real-life study evaluated the effect of six AITs (native pollen SLIT/SCIT, four allergoid SCITs) vs symptomatic medication use, on AR symptoms and asthma symptoms/onset, in patients with birch pollen-associated AR and/or asthma. METHODS: In this retrospective cohort analysis of a German longitudinal prescription database, AIT patients received ≥2 successive seasonal treatment cycles; non-AIT patients had ≥3 AR prescriptions in three seasons or previous month. Patients were matched for: index year, age, gender, main indication at index, number of seasonal cycles within treatment period, baseline AR/asthma treatment prescriptions. Multiple regression analysis compared prescription data in AIT and non-AIT groups as proxy for clinical status/disease progression. RESULTS: Up to 6 years of follow-up, significantly more AIT (65.4%) vs non-AIT (47.4%) patients were AR medication-free; odds ratio (OR) [95% confidence interval (CI)]: 0.51 [(0.48-0.54); P < 0.001] (28.6% covariate-adjusted reduction vs non-AIT; P < 0.001), and significantly more AIT (49.1%) vs non-AIT (35.1%) patients were asthma medication-free [OR (95% CI): 0.59 (0.55-0.65); P < 0.001] (32% reduction vs non-AIT; P < 0.001), or reduced existing asthma medication use (32% covariate-adjusted reduction vs non-AIT; P < 0.001). During treatment, new-onset asthma risk was significantly reduced in the AIT vs non-AIT group (OR: 0.83; P = 0.001). CONCLUSIONS: Birch pollen AIT demonstrated real-world benefits up to 6 years post-treatment cessation through significantly reduced AR and asthma medication intake, and significantly decreased risk of new-onset asthma medication use on-treatment.

Long-term effect of monophosphoryl lipid A adjuvanted specific immunotherapy in patients with grass pollen allergy.

BACKGROUND: Ultra-short course pollen immunotherapy adjuvanted with monophosphoryl lipid A (MPL) is attractive to conventional allergen-specific immunotherapy (AIT). Long term efficacy of MPL-AIT has not been evaluated. METHODS: 68 patients (age 16.75 ± 5.3 years) with allergic rhinitis to grass pollen were investigated. Group 1: 21 controls; Group 2: 19 after complete AIT, and Group 3: 28 with AIT and treatment cessation: 4 years range 3-6 years ago. RESULTS: The clinical symptoms (running nose, sneezing, conjunctivitis and the weekly overall score) were significantly reduced in patients group 2 and 3 compared with controls without AIT p < 0.0001. T-regulatory cells and TH1/TH2 cytokine pattern did not differ between patient groups. CONCLUSION: The patients in our trial with grass pollen allergy exhibited significant and long-lasting improvements after MPL-AIT, however larger trials are needed to support this finding.

Grass pollen sublingual immunotherapy tablets provide long-term relief of grass pollen-associated allergic rhinitis and reduce the risk of asthma: findings from a retrospective, real-world database subanalysis.

BACKGROUND: We assessed real-world, long-term effectiveness of two marketed sublingual immunotherapy (SLIT) tablets for allergic rhinitis (AR), and their impact on allergic asthma (AA) onset/progression. METHODS: Retrospective, longitudinal German prescription database subanalysis of AR patients receiving 5- or 1-grass pollen SLIT tablets (n = 1,466/1,385), versus patients not using allergy immunotherapy (AIT) (n = 71,275). Primary endpoint: change over time in AR symptomatic medication prescriptions after treatment cessation; secondary endpoints: new asthma onset, and change over time in asthma medication prescriptions during treatment/follow-up periods. RESULTS: Mean number of AR medication prescriptions was significantly decreased during follow-up (of up to 6 years) with both SLIT tablets versus the non-AIT group (p < 0.001). Over the full-analysis period, proportions of patients with new-onset asthma were 8.8% (odds ratio: 0.676, p = 0.011), 10.3% (odds ratio: 0.720, p = 0.060) and 11.6% in the 5- and 1-grass pollen SLIT tablet and non-AIT groups, respectively. For all treatment-analysis periods, both SLIT tablet groups were associated with fewer asthma medication prescriptions versus non-AIT controls. CONCLUSIONS: These findings confirm the real-world benefits of 5- and 1-grass-pollen SLIT tablets in slower AR progression, reduced risk of new asthma onset in the non-asthmatic population, and slower asthma progression in the asthmatic population.

Combinations of distinct long-chain polyunsaturated fatty acid species for improved dietary treatment against allergic bronchial asthma.

Allergic bronchial asthma is a chronic inflammatory disease of the airways with an increasing incidence in Western societies. Exposure to allergens provokes recurrent attacks of breathlessness, airway hyperreactivity, wheezing, and coughing. For the early phase and milder forms of allergic asthma, dietary supplementation with long-chain polyunsaturated fatty acids (LCPUFA), predominantly fish oil-associated eicosapentaenoic (C20:5 ω-3) and docosahexaenoic acid (C22:6 ω-3), and distinct crop oil-derived fatty acids might provide a sustainable treatment strategy, as discussed in several studies. In addition to immune-controlling prostaglandins, leukotrienes, and thromboxanes, specialized proresolving mediators, such as lipoxins, resolvins, protectins, and maresins, are metabolized from different LCPUFA, which actively resolve inflammation. The aim of this review was to discuss the possible synergistic effects of ω-3 and ω-6 LCPUFA combinations concerning rebuilding fatty acid homeostasis in cellular membranes, modifying eicosanoid metabolic pathways, controlling inflammatory processes by focusing on resolving inflammation in the bronchoalveolar system on the cellular level, and helping to control clinical symptoms in bronchial asthma.

Transient impact of omalizumab in pollen allergic patients undergoing specific immunotherapy.

BACKGROUND: Recently, we showed that combination of omalizumab with specific immunotherapy (SIT) for treatment of patients with seasonal allergic rhinitis (SAR) and comorbid seasonal allergic asthma (SAA) is safe and reduced the symptom load in a statistically significant and clinically meaningful manner during the first pollen season. OBJECTIVE: The aim of this study was to investigate long-lasting effects of an initial combination treatment with SIT+omalizumab, a monoclonal anti-IgE antibody, in a follow-up period with SIT treatment only in patients with SAR and comorbid SAA incompletely controlled by conventional pharmacotherapy. METHODS: A randomized, double-blind, placebo-controlled, multicenter trial was performed to assess the efficacy and safety of omalizumab (Xolair(®)) vs. placebo in combination with SIT (depigmented allergoid vaccine, Depigoid(®)) during the first grass pollen season. Omalizumab or placebo therapy was started 2 wk before SIT; the whole treatment lasted 18 wk. After the first pollen season, SIT was given for two subsequent years without omalizumab. Primary end-point was daily 'symptom load', the sum of daily scores for symptom severity and rescue medication use in the second and third year. RESULTS: A total of 140 patients (age 11-46 yr) were randomized; 130, 128, and 114 patients finished the study after 1, 2, and 3 yr, respectively. The main efficacy variable was the mean daily symptom load as assessed in the patients' diary. No systematic differences between both analysis groups were detected in the findings from symptom load, symptom severity score, or rescue medication score. Further subjective data did not show differences between both groups in the quality-of-life data as assessed with the ACQ, AQLQ, and the RQLQ. Investigators' assessment of treatment effectiveness in the first and second year of study extension showed more patients with favorable long-term treatment outcome ('excellent' and 'good') in the SIT plus omalizumab group than in the SIT plus placebo group. In line with these findings, FEV1 improved at the end of both years in the group which was treated with the combination therapy in the double-blind study compared with the Depigoid plus placebo group. CONCLUSION: Eighteen weeks' treatment of omalizumab in combination with SIT in patients with SAR and comorbid SAA reduced the symptom load during the treatment period but showed no prolonged effect during treatment with SIT only. A slight increase in lung function (FEV1) in patients formerly treated with the omalizumab/SIT combination therapy should encourage further evaluation of long-term effects of omalizumab.

Pollinex Quattro: an innovative four injections immunotherapy in allergic rhinitis.

The prevalence of seasonal allergic rhinitis in the western world is high and increasing. Besides considerably affecting physical and psychosocial aspects of patients' lives, allergic rhinitis is often associated with allergic asthma and may aggravate this condition over time. Specific immunotherapy is currently the only approved therapy that can modify the underlying disease process and induce long-term tolerance to allergens. Pollinex Quattro is a subcutaneous four injections immunotherapy consisting of tyrosine-absorbed specific allergoids and enhanced with the adjuvant monophosphoryl lipid A (MPL(®)). MPL(®) induces a significant Th 1-type immune response, characterized by an increase of allergen-specific IgG antibody levels and dampening of the IgE response during allergen exposure. Due to this dual action of stimulating the immune system, Pollinex Quattro is clinically effective after only four injections given pre-seasonally. A large clinical program has demonstrated efficacy and tolerability of Pollinex Quattro in children, adolescents and adults with grass and tree pollen allergy. A health economics study concluded that an immunotherapy with only 4 injections might be more cost-beneficial than other application forms of immunotherapy.

Bronchial allergen challenge using the Medicaid dosimeter.

BACKGROUND: Bronchial allergen provocations are well established in asthma research. We evaluated the reproducibility of single-concentration, single-step allergen challenges in volunteers with grass pollen allergy. METHODS: Forty-seven subjects underwent bronchial challenges using the aerosol provocation system nebulizer (Medicaid Sidestream) with incremental doses of grass pollen to define the individual allergen dose that causes a 20% drop in FEV(1) (PD(20)FEV(1)). In 39 subjects this procedure was followed by single-step challenges. Early and late asthmatic responses were monitored, and increases in exhaled nitric oxide were measured before and 24 h after single-step challenges. RESULTS: After the first single-step challenge, the maximum drop in FEV(1) was 21.3% ± 8.0. A comparison of the drop in FEV(1) to the initial incremental challenge (29.7% ± 7.5) revealed an intraclass correlation of -0.30 (p < 0.05). In the second single-step challenge, the mean drop in FEV(1) was 20.9% ± 7.2. Compared with the first single-step challenge, the intraclass correlation was 0.37 (p < 0.05) and the 95% limits of agreement according to Bland and Altman were -17.5 to 18.1%. The increases in exhaled nitric oxide revealed substantial agreement in repeated single-step challenges (26.8 ppb ± 27.8 and 21.8 ppb ± 21.9, ICC 0.62, p < 0.001). CONCLUSIONS: The use of aerosol provocation system to calculate the PD(20)FEV(1) allergen is a timesaving procedure and is less prone to errors because only one dilution of the allergen is used. The repeatability in well-defined subjects is excellent to study the mechanisms of allergen-induced airway inflammation and the development of new treatments for allergic diseases.

Safety, tolerability, and impact on allergic inflammation of autologous E.coli autovaccine in the treatment of house dust mite asthma--a prospective open clinical trial.

BACKGROUND: Asthma is increasing worldwide and results from a complex immunological interaction between genetic susceptibility and environmental factors. Autovaccination with E. coli induces a strong TH-1 immune response, thus offering an option for the treatment of allergic diseases. METHODS: Prospective open trial on safety, tolerability, and impact on allergic inflammation of an autologous E.coli autovaccine in intermittent or mild persistent house dust mite asthma. Determination of exhaled nitric monoxide (eNO) before and after bronchial mite challenge initially and after nine months of autovaccination. RESULTS: In nine subjects and a total of 306 injections, we observed 101 episodes of local erythema (33.3%; median of maximal diameter 2.5 cm), 95 episodes of local swelling (31.1%; median of maximal diameter 3 cm), and 27 episodes of local pain (8.8%). Four subjects reported itching at the injection site with a total of 30 episodes (9.8%). Median eNO increase after autovaccination was significantly smaller (from 27.3 to 33.8 ppb; p = 0.334) compared to initial values (from 32.6 to 42.2 ppb; p = 0.046) (p = 0.034). We observed no serious adverse events. All organ functions (inclusive electrocardiogramm) and laboratory testing of the blood (clinical chemistry, hematology) and the urine (screening test, Β-microglobuline) were within normal limits. Vital signs undulated within the physiological variability. CONCLUSION: The administration of autologous autovacine for the treatment of house dust mite asthma resulted in a reduction of the eNO increase upon bronchial mite challenge. In nine subjects and 306 injections, only a few mild local reactions and no systemic severe adverse events were observed. TRIAL REGISTRATION: EudraCT Nr. 2005-005534-12ClinicalTrials.gov ID NCT00677209.

Omega-3 polyunsaturated fatty acids and bronchial inflammation in grass pollen allergy after allergen challenge.

UNLABELLED: RATIO: Asthma is a major public health problem, with bronchial inflammation as the therapeutic target. The role of dietary fish oil derived polyunsaturated fatty acids (PUFAs) in allergic inflammation is controversial. Most asthmatics suffer from mild disease and non-pharmacologic interventions are attractive. This study investigates the anti-inflammatory potential of nutritional PUFAs in an experimentally induced bronchial inflammation. METHODS: We examined 38 grass pollen allergic asthmatics and 19 controls. History of dietary PUFA intake was compared with levels of PUFAs in erythrocyte membranes, and stratified according to low (25th quartile; Q25) and high (75th quartile; Q75) ratios of omega-3 (n-3) to omega-6 (n-6) PUFAs as a surrogate for anti-inflammatory (Q75) or proinflammatory (Q25) effects. Bronchial inflammation was simulated with one-step inhalation of grass pollen. Bronchial response (exhaled nitric monoxide, eNO as surrogate for inflammation, decrease of FEV(1)) was correlated with levels of PUFAs in erythrocyte membranes. RESULTS: Ratios of n-3/n-6 PUFA were significantly lower in asthmatics than in healthy controls. Levels of eNO were significantly higher in Q25 asthmatics than in Q75 asthmatics (p = 0.040). There was a trend of higher bronchial hyperreactivity in Q25 asthmatics (median PD(20) 0.27 vs. 0.14; n.s.), induced by specific bronchial challenge with grass pollen (FEV(1) decrease 16.7 vs. 23.1%; n.s.). CONCLUSION: When stratifying for erythrocyte membrane PUFA content as a surrogate for alimentary intake, we found mild effects on bronchial allergic inflammation. Future intervention studies with pharmacological PUFA doses appear suitable to clarify dietary PUFA role as an adjunctive intervention to the established treatment of asthma. ClinicalTrials.gov No. NCT00519740.

Safety of anti-IgE treatment with omalizumab in children with seasonal allergic rhinitis undergoing specific immunotherapy simultaneously.

INTRODUCTION: Seasonal allergic rhinitis (SAR) affects at least 10-25% of the Caucasian race and about 40% of patients are children. Standard treatment of SAR is specific immunotherapy (SIT), but anti-allergic drugs can significantly enhance efficacy of SIT. One candidate is the humanized monoclonal anti-IgE antibody omalizumab. MATERIAL AND METHODS: Randomized, double-blind, placebo-controlled, multi-centre trial in Germany. A total of 221 children were randomly assigned to four different groups and treated with SIT (either grass or birch pollen), starting at least 14 wk before the local birch pollen season. After the 12-wk SIT titration phase, either anti-IgE (omalizumab) or placebo (NaCl 0.9%) therapy was added. This combination therapy with SIT and anti-IgE or placebo lasted 24 wk. To record local reactions and adverse events (AE), the injection site was examined by a clinician 20 min after application of study medication. Further, patients stated any AE and the use of rescue medication by means of a diary 3 days after every injection. Finally, any AE or serious adverse event (SAE) reported by the patients was specified on a standard form by clinicians. Overall tolerance was judged by the doctors according to the patient's diaries. To test differences between the groups, we used either the two-sided Wilcoxon rank-sum test or the two-sided chi-square test. RESULTS: Tolerability of SIT and omalizumab treatment was good (82% of patients). Only some AE with possible causal relationship to treatment occurred slightly more often in the verum groups, i.e. local reactions (16.8 vs. 12.3%) and gastrointestinal (2.7 vs. 0.9%) and ear symptoms (1.8 vs. 0%). Most AE (93.4% in omalizumab and 87.2% in placebo group) were judged by the patients as mild to moderate. SAE were restricted to four patients with asthma in the placebo group, two subjects with headache in the verum group and three patients with infections (two in verum and one in placebo group). Only the cases of asthma were judged to be possibly related to study medication. Further, redness and swelling at the SIT injection site appeared significantly more often in the placebo group which suggests a positive effect of omalizumab on local reaction induced by SIT. CONCLUSION: Omalizumab represents an important clinical advance in the management of allergic diseases and can be considered to be safe in children.

Influence of low-dose polyunsaturated fatty acids supplementation on the inflammatory response of healthy adults.

OBJECTIVE: The aim of the present study was to examine the immune-modulating effect of two different fat blends enriched with a low dose of anti- or proinflammatory polyunsaturated fatty acids on the fatty acid status and subsequently on the immune response of healthy volunteers. METHODS: Thirty healthy volunteers were randomly assigned to group A (anti-inflammatory blend rich in polyunsaturated fatty acids: alpha-linolenic acid, 240 mg/d; eicosapentaenoic acid, 120 mg/d; stearidonic acid, 49 mg/d; and gamma-linolenic acid, 73 mg/d) or group B (arachidonic acid, 40 mg/d; containing an inflammatory fat blend) for a 2-wk dietary supplementation period. Concentrations of interleukin-8, interleukin-10, tumor necrosis factor-alpha, prostaglandins E(1) and E(2), and leukotriene B(4) were investigated before, after 2 wk of supplementation, and 2 wk after stopping supplementation using a whole blood ex vivo lipopolysaccharide-stimulation assay. RESULTS: Plasma concentrations of alpha-linolenic acid and eicosapentaenoic acid were significantly increased in group A. In addition, dietary fat blends influenced eicosapentaenoic acid concentration in erythrocyte membranes. Supplementation of the fat blends resulted in contrasting effects on the expression of lipid mediators and cytokines after ex vivo lipopolysaccharide stimulation. Release of prostaglandin E(1) and leukotriene B(4) were significantly decreased in group A, whereas prostaglandin E(2) and interleukin-10 concentrations were significantly increased in group B. No effect on interleukin-8 or tumor necrosis factor-alpha release was found after supplementation with either fat blend. CONCLUSIONS: These results show an immune-modulating effect of a low-dose dietary polyunsaturated fatty acid supplementation. However, further studies regarding fat-blend composition and period of supplementation in patients with inflammatory conditions are required.

Impact of early dietary gamma-linolenic acid supplementation on atopic eczema in infancy.

Polyunsaturated fatty acids (PUFAs) are components of cell membranes and may play an immunomodulating role in the pathogenesis of atopic dermatitis (AD). The goal was to determine the impact of PUFAs on AD by dietary supplementation of infants. Based on the parents' decision on their babies' primary feeding, mothers and newborns were randomized to the supplementation with gamma-linolenic acid (GLA) or placebo for up to 6 months. Breastfed infants received GLA by supplementing their mothers. Formula diet was commercial whey hydrolysate unsupplemented with PUFAs. Of 131 eligible infants, 24 developed AD within the first year of life. Of these, nine belonged to the exclusively breastfed group (n = 58), 14 to the combined-fed group (n = 53), and one to the never breastfed group (n = 20). We could not find an influence of GLA on the development of AD. In subjects with AD, at 1 yr of age the serum-immunoglobulin E (IgE) was the lowest in the GLA-supplemented group A-subjects. In the GLA-supplemented group, GLA-levels in breast milk were similar in atopic and non-atopic infants. In the non-supplemented group the GLA-content of breast milk was 0.07% of total fatty acids in atopic infants vs. 0.17% in non-atopic infants (p < 0.01). Dietary GLA-supplementation could not prevent AD. Interestingly, the number of infants developing AD was the lowest in never breastfed children. In infants suffering from AD, GLA-supplementation seemed to reduce total IgE in the first year of life.

Efficacy of combination treatment with anti-IgE plus specific immunotherapy in polysensitized children and adolescents with seasonal allergic rhinitis.

BACKGROUND: Specific immunotherapy (SIT) and treatment with monoclonal anti-IgE antibody have complementary modes of action. OBJECTIVE: The purpose of this study was to determine whether combined therapy could provide better efficacy than either treatment alone. METHODS: We conducted a randomized, double-blinded trial to assess the efficacy and safety of subcutaneously administered anti-IgE (omalizumab) or placebo in children and adolescents with seasonal allergic rhinitis in both a birch pollen season and a grass pollen season (sequential seasons together lasting an average of 84 days). There were 4 treatment arms. Each subject was started on SIT-birch or SIT-grass, and anti-IgE or placebo was started before and maintained during the anticipated pollen seasons (a total of 24 weeks). The primary efficacy variable was symptom load, the sum of daily symptom severity score plus rescue medication use. RESULTS: A total of 221 subjects (intent-to-treat population) aged 6 to 17 years were analyzed for efficacy. Combination therapy reduced symptom load over the 2 pollen seasons by 48% (P <.001) over SIT alone. When analyzed separately by season, the 2 groups receiving unrelated SIT were considered placebo controls. In the grass season, symptom loads were as follows: unrelated (birch) SIT + placebo, 0.89 (reference value); unrelated (birch) SIT + anti-IgE, 0.49 (-45%); SIT-grass + placebo, 0.61 (-32%); SIT-grass + anti-IgE, 0.26 (-71%). CONCLUSION: Anti-IgE therapy conferred a protective effect independent of the type of allergen. Additional clinical benefit was demonstrated in both pollen seasons, whether there was coverage by SIT or not. This combination might prove useful for the treatment of allergic rhinitis, particularly for polysensitized patients.